This invention relates to the field of nutrition, and more particularly to parenteral nutrition via peripheral veins.
Total parenteral nutrition (TPN) is a recent advance in the maintenance of patients having an impaired gastrointestinal capacity. Such patients may have lost the use of a large portion of their intestinal tract, either permanently due to surgical intervention as may be required in cancer or Crohn's disease, or temporarily as a result of chemotherapeutic drugs or in the treatment of diverticulitis. Objectives of TPN include administering all of the patient's requirements of calories and essential nutrients directly into the circulatory system, bypassing the digestive tract entirely, or administering nutrients to the remnant digestive tract in a form that will provide as much nutrition as possible without injuring either the circulatory system or the intestines.
A major difficulty in TPN has been the sensitivity of the intestines or vasculature to contact with nutrient solutions having high osmolarity. To date, it has been necessary to use such highly concentrated solutions because at lower concentrations the nutrient solutions supply insufficient calories before exceeding the patient's ability to deal with excess diluent. Generally, a patient must receive at least 2500 ml daily of a 20% glucose solution to reach the 2000 minimum calories required, and caloric requirements can be greater in many stressed patients.
Attempts to deal with this problem have included infusing the solution via a central venous catheter. A catheter is threaded from a peripheral vein in an arm or a leg, for example, into the vena cava. Highly concentrated nutrient solutions can be passed through the catheter into the large volume of central venous blood, where rapid dilution of the solution obviates vascular injury and reduces local hemolysis. Central venous catheters, however, among other disadvantages require a special procedure to insert. It would be safer and considerably more convenient if parenteral nutrition could be administered via a peripheral vein.
Calorie sources for infusion which are alternate or supplemental to glucose, amino acids or lipid emulsions have been previously suggested or disclosed. See Birkhahn, R. et al., "J. Par. Ent. Nutr." 5(1):24-31 (1981); Birkhahn, R. et al., "Am. J. Clin. Nutr.", 30: 2078-2082 (1977); Birkhahn, R. et al., "Am. J. Clin. Nutr." 31:436-441 (1978); Birkhahn, R. et al., "J. Nutr." 109:1168-1174 (1979); Birkhahn, R. et al., "J. Par. Ent. Nutr." 3(5):346-349 (1979); LeVeen, H., "Am. J. Dig. Dis." 17:20 (1950); LeVeen, H., "Am. J. Clin. Nutr." 5:251 (1957) and Milner, U.S. Pat. No. 3,928,135. None of the compounds have proven entirely satisfactory, especially for peripheral vein infusion. The principal difficulties have included insufficient calorie density for peripheral infusion, incomplete metabolism of the compounds, toxic metabolites, side effects, and insufficient water solubility.
Accordingly, the objectives of this invention include:
(a) providing compounds for parenteral or enteral nutrition which are biologically available;
(b) providing compounds having a biologically available caloric content in considerable excess of glucose;
(c) providing compounds which are nontoxic to the vasculature, the intestines and the cellular elements of the blood, in particular compounds which exhibit insufficient surfactant properties to hemolyze or otherwise damage erythrocytes;
(d) providing compounds which can be dissolved in solutions to yield infusates having improved calorie density;
(e) providing and administering to patients the above compounds in conventional parenteral solution containers along with other nutrients such as vitamins, electrolytes, trace metals and amino acids; and
(f) providing compounds which are hydrolyzed by the tissues or intestinal flora to substrates of oxidative metabolism.
These and other objects will be apparent from consideration of this specification as a whole.